The purpose of this project is to transplant human pancreatic islet tissue either as free grafts of dispersed islet tissue or as immediately vascularized intact segmental pancreatic grafts. We have tested the ability of free grafts of dispersed islet tissue to ameliorate diabetes in both the allograft and autograft situation. Allogeneic transplants of dispersed pancreatic islet tissue have not resulted in cure of diabetes, failure being due to either rejection or to technical problems. However, the feasibility of transplanting dispersed pancreatic islet tissue as a free graft has been shown in the autograft situation. Nine patients with chronic pancreatitis have been subjected to total pancreatectomy and islet autotransplantation. Diabetes was completely obviated in one patient, was partially ameliorated in two patients (do not need exogenous insulin), and was unsuccessful or partially successful in the other patients, the partial successes being the individuals that have detectable C-peptide levels and a nonketosis prone type of diabetes. At this point, the most efficient technique of transplanting pancreatic islet tissue is as an intact immediately vascularized segmental pancreatic graft. Eleven diabetic patients have received grafts of this type six months to six years after successful kidney transplantation. Three patients currently have functioning grafts and are normoglycemic without the need for exogenous insulin 3, 8 and 19 months. Three patients rejected the grafts at 2, 3 and 4 months. Three patients had their grafts fail for technical reasons, but they are alive and well and two patients died one and two months after transplantation of viral infections. The patients with successful grafts as subjects of metabolic studies and long term studies to determine the effect on the secondary complications of diabetes. It is projected that 10 to 15 diabetic patients a year will recieve pancreatic islet transplants.